Skin permeability barrier formation by the ichthyosis-causative gene <i>FATP4</i> through formation of the barrier lipid ω- <i>O</i> -acylceramide
Haruka Yamamoto, Miku Hattori, Waleé Chamulitrat, Yusuke Ohno, Akio Kihara
Abstract
Significance Acylceramide is essential for skin permeability barrier formation. However, its biosynthesis pathway has not yet been elucidated in its entirety. In the present study, we found that Fatp4 disruption substantially decreased the amount of acylceramides in mice, as did FATP4 knockdown in human keratinocytes. In addition, in vitro experiments demonstrated that FATP4 exhibited acyl-CoA synthetase activity toward an ω-hydroxy ultra-long-chain fatty acid, an intermediate of the acylceramide biosynthetic pathway. From these results, we conclude that FATP4 functions in skin barrier formation through acylceramide synthesis. Our findings not only reveal the pathogenic mechanism of ichthyosis prematurity syndrome, but also help to elucidate the molecular mechanism of the synthesis of the skin barrier lipid acylceramide.